Focused Ultrasound Stimulates the Prefrontal Cortex and Prevents MK-801-Induced Psychiatric Symptoms of Schizophrenia in Rats
Tsung-Yu Pan, Yi-Ju Pan, Shih-Jen Tsai, Che-Wen Tsai, Feng-Yi Yang
Schizophrenia Bulletin 2024, 50, 120-131 · 10.1093/schbul/sbad078
Abstract
Background and hypothesis Treatment of schizophrenia remains a major challenge. Recent studies have focused on glutamatergic signaling hypoactivity through N-methyl-D-aspartate (NMDA) receptors. Low-intensity pulsed ultrasound (LIPUS) improves behavioral deficits and ameliorates neuropathology in dizocilpine (MK-801)-treated rats. The aim of this study was to investigate the efficacy of LIPUS against psychiatric symptoms and anxiety-like behaviors. Study design Rats assigned to 4 groups were pretreated with or without LIPUS for 5 days. The open field and prepulse inhibition tests were performed after saline or MK-801 (0.3 mg/kg) administration. Then, the neuroprotective effects of LIPUS on the MK-801-treated rats were evaluated using western blotting and immunohistochemical staining. Study results LIPUS stimulation of the prefrontal cortex (PFC) prevented deficits in locomotor activity and sensorimotor gating and improved anxiety-like behavior. MK-801 downregulated the expression of NR1, the NMDA receptor, in rat medial PFC (mPFC). NR1 expression was significantly higher in animals receiving LIPUS pretreatment compared to those receiving only MK-801. In contrast, a significant increase in c-Fos-positive cells in the mPFC and ventral tegmental area was observed in the MK-801-treated rats compared to those receiving only saline; this change was suppressed by pretreatment with LIPUS. Conclusions This study provides new evidence for the role of LIPUS stimulation in regulating the NMDA receptor and modulating c-Fos activity, which makes it a potentially valuable antipsychotic treatment for schizophrenia.
Abstract via europepmc.
Exposures
Exposure 1: LIPUS to prefrontal cortex (PFC), daily pretreatment for 5 days
Target: prefrontal cortex — “prefrontal cortex (PFC)”
Device: Mettler · Mettler Electronics · ME740 generator with ME7413 plane transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Ispta, domain unspecified (W/cm²) | 0.5 | ✓?⚑ |
The duration of each sonication was 5 minutes, with a 5-minute interval between each sonication; the total sonication time of the LIPUS stimulation was 15 minutes every day, delivered daily for 5 days to the PFC (3.0 mm anterior to bregma), while animals were anesthetized with 2% isoflurane.
Flags from extraction
exposures[0].unspecified_domain.ispta_w_cm2— Paper reports '500 mW/cm2 spatial average intensity over the plane transducer head', which does not clearly correspond to either spatial-peak pulse-average (ISPPA) or spatial-peak temporal-average (ISPTA) intensity as defined in this schema; assigned to ISPTA as the closer match (both are time-averaged metrics) but the terminology mismatch should be checked against source. Domain (free field vs in situ) is also not stated.n_subjects— Figure legends report different per-group n's for different outcomes (n=10 per group for behavioral tests in Figure 1; n=5 per group for immunofluorescence/western-blot outcomes in Figures 2-5); only 2 of the 4 groups (LIPUS, LIPUS+MK-801) actually received active ultrasound, but the paper does not give a single total count of ultrasound-exposed animals.anaesthesia— Animals were anesthetized (2% isoflurane) during LIPUS delivery, but behavioral testing (open field, PPI) was conducted afterward with no anesthesia mentioned; classified as 'both' since the paper describes an anesthetized delivery procedure but presumably awake behavioral assessment.adverse_events— Paper does not include an explicit statement about adverse events or safety monitoring for the LIPUS procedure.